| Human cytomegalovirus glycoproteins gB and gH/gL mediate epithelial cell-cell fusion when expressed either in cis or in trans. | |
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MedLine Citation:
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PMID: 18815310 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Herpesviruses use a cascade of interactions with different cell surface molecules to gain entry into cells. In many cases, this involves binding to abundant glycosaminoglycans or integrins followed by interactions with more limited cell surface proteins, leading to fusion with cellular membranes. Human cytomegalovirus (HCMV) has the ability to infect a wide variety of human cell types in vivo. However, very little is known about which HCMV glycoproteins mediate entry into various cell types, including relevant epithelial and endothelial cells. For other herpesviruses, studies of cell-cell fusion induced by viral proteins have provided substantial information about late stages of entry. In this report, we describe the fusion of epithelial, endothelial, microglial, and fibroblast cells in which HCMV gB and gH/gL were expressed from nonreplicating adenovirus vectors. Fusion frequently involved the majority of cells, and gB and gH/gL were both necessary and sufficient for fusion, whereas no fusion occurred when either glycoprotein was omitted. Coexpression of UL128, UL130, and UL131 did not enhance fusion. We concluded that the HCMV core fusion machinery consists of gB and gH/gL. Coimmunoprecipitation indicated that HCMV gB and gH/gL can interact. Importantly, expression of gB and gH/gL in trans (gB-expressing cells mixed with other gH/gL-expressing cells) resulted in substantial fusion. We believe that this is the first description of a multicomponent viral fusion machine that can be split between cells. If gB and gH/gL must interact for fusion, then these molecules must reach across the space between apposing cells. Expression of gB and gH/gL in trans with different cell types revealed surface molecules that are required for fusion on HCMV-permissive cells but not on nonpermissive cells. |
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Authors:
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Adam L Vanarsdall; Brent J Ryckman; Marie C Chase; David C Johnson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-09-24 |
Journal Detail:
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Title: Journal of virology Volume: 82 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-12 Completed Date: 2008-11-25 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 11837-50 Citation Subset: IM |
Affiliation:
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Dept. of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Fusion* Cell Line Epithelial Cells / cytology Humans Immunoprecipitation Membrane Glycoproteins / physiology Viral Envelope Proteins / chemistry, physiology* Viral Proteins / chemistry, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI055051/AI/NIAID NIH HHS; EY11245/EY/NEI NIH HHS; F32-EY015965/EY/NEI NIH HHS; T32-AI07472/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/UL115 protein, Human herpesvirus 5; 0/UL128 protein, human cytomegalovirus; 0/Viral Envelope Proteins; 0/Viral Proteins; 0/glycoprotein B, Simplexvirus; 0/glycoprotein H, Cytomegalovirus |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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